DS-8201a in HER2-positive Gastric Cancer That Cannot Be Surgically Removed or Has Spread (DESTINY-Gastric02)

A Phase 2, Open-label, Single-arm Trial of Trastuzumab Deruxtecan (DS 8201a) in HER2-positive, Unresectable or Metastatic Gastric or Gastro-esophageal Junction (GEJ) Adenocarcinoma Subjects Who Have Progressed on or After a Trastuzumab-containing Regimen (DESTINY-Gastric02)

This study will find out if trastuzumab deruxtecan is safe and works for participants with gastric or gastroesophageal junction cancer.

They must have human epidermal growth factor receptor 2 (HER2)-positive gastric or gastro-esophageal junction (GEJ) cancer:

• that cannot be removed surgically
• that has moved to other parts of the body
• that got worse during or after treatment that included trastuzumab

The study will enroll about 80 participants. Sites will be in North America and the European Union.

Study Overview

• Status: Completed
• Conditions: Adenocarcinoma Gastric Stage IV With Metastases; Adenocarcinoma - GEJ
• Intervention / Treatment: Drug: Trastuzumab deruxtecan

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • UCL St-Luc
  • Haine-Saint-Paul, Belgium, 7100
    • Hopital de Jolimont
  • Leuven, Belgium, 3000
    • UZ Leuven
• Italy
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milano, Italy, 20162
    • ASST Grande Ospedale Metropolitano Niguarda
  • Modena, Italy, 41124
    • Azienda Ospedaliero Universitaria Di Modena Policlinico
  • Padua, Italy, 35128
    • Oncology Institute Veneto IOVIRCCS
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (VHIO)
  • Barcelona, Spain, 8908
    • Institut Catalan de Oncologia Hospital Duran i Reynals
  • Madrid, Spain, 28046
    • Hospital La Paz
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro
  • Valencia, Spain, 46010
    • Biomedical Research Institute Hospital de Valencia
• United Kingdom
  • Cambridge, United Kingdom, CB2 0RE
    • Cambridge University Hospitals NHS Foundation Trust
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden Hospital
  • Manchester, United Kingdom, M20 4BX
    • Christie Hospital
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center Hospital
    • Monterey, California, United States, 93940
      • Pacific Cancer Care
    • Santa Monica, California, United States, 90404
      • UCLA Health
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • Meriden, Connecticut, United States, 06451
      • Midstate Medical Center
    • New Britain, Connecticut, United States, 06052
      • The Hospital of Central Connecticut
    • New Haven, Connecticut, United States, 06511
      • Smilow Cancer Hospital at Yale-New Haven
  • Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute, Baptist Health South Florida
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center UCMC Duchossois Center for Advanced Medicine DCAM
  • Kansas
    • Kansas City, Kansas, United States, 66205
      • Kansas University Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital (MGH)
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center (BIDMC)
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Alvin J. Siteman Cancer Center Washington University
  • New York
    • Lake Success, New York, United States, 11042
      • Northwell Health Cancer Institute
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Health Network
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Md Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington/Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men or women ≥18 years old (local regulatory guidelines apply)
• Has pathologically documented HER2-positive gastric or GEJ cancer that is unresectable or metastatic, and that progressed during or after treatment regimen containing trastuzumab
• Has at least one measurable lesion per RECIST v1.1, as confirmed by investigator review
• If of reproductive potential, agrees to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 7 months for females and 4 months for males after the last dose of study drug

Exclusion Criteria:

• Has had anticancer therapy after first-line treatment regimen containing trastuzumab
• Has uncontrolled cardiovascular disease, including any of the following: history of myocardial infarction (MI) within 6 months of first dose or symptomatic congestive heart failure (New York Heart Association Class II to IV), troponin levels consistent with MI as defined according to the manufacturer within 28 days of first dose, or corrected QT interval (QTc) prolongation to >470 ms (females) or >450 ms (male) based on screening triplicate 12-lead electrocardiogram (ECG)
• Has history of non-infectious interstitial lung disease (ILD)/pneumonitis that required corticosteroid therapy, or current ILD/pneumonitis that cannot be ruled out at screening
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of the first dose, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy.
• Has pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART)
• Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms (Note: participants with clinically inactive brain metastases may be included in the study as well as participants with treated brain metastases who are no longer symptomatic and no longer require treatment with corticosteroids or anticonvulsants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: All participants; Participants who have centrally confirmed HER2-positive gastric or gastro-esophageal junction cancer will be treated with trastuzumab deruxtecan by intravenous (IV) infusion every 3 weeks, until progression of disease or withdrawal from treatment for other reasons.	Drug: Trastuzumab deruxtecan; Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion; Other Names: DS-8201a

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response Rate (ORR) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma	The Objective Response Rate (ORR) was the defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by independent central review (ICR) committee based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR based on ICR is reported.	Up to 16 months (data cut-off)
Percentage of Participants With Objective Response Rate (ORR) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma	The Objective Response Rate (ORR) was the defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by independent central review (ICR) committee based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR based on ICR is reported.	Up to 23 months (data cut-off)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma	Progression-free survival (PFS) by independent central review was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.	Up to 16 months (data cut-off)
Progression-Free Survival (PFS) Based on Investigator Assessment Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma	Progression-free survival (PFS) by investigator assessment was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.	Up to 16 months (data cut-off)
Objective Response Rate (ORR) Based on Investigator Assessment Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma	The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by investigator assessment based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR based on investigator assessment is reported.	Up to 16 months (data cut-off)
Overall Survival (OS) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma	Overall survival (OS) was defined as the time from the date of first dose of study drug to the date of death due to any cause.	Up to 16 months (data cut-off)
Duration of Response (DoR) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma	Duration of Response (DOR) was defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DoR based on independent central review.	Up to 16 months (data cut-off)
Progression-Free Survival (PFS) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma	Progression-free survival (PFS) by independent central review was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.	Up to 23 months (data cut-off)
Objective Response Rate (ORR) Based on Investigator Assessment Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma	The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by investigator assessment based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR based on investigator assessment is reported.	Up to 23 months (data cut-off)
Overall Survival (OS) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma	Overall survival (OS) was defined as the time from the date of first dose of study drug to the date of death due to any cause.	Up to 23 months (data cut-off)
Duration of Response (DoR) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma	Duration of Response (DOR) was defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DoR based on independent central review.	Up to 23 months (data cut-off)

Collaborators and Investigators

• Sponsor: Daiichi Sankyo
• Collaborators: AstraZeneca
• Investigators: Study Director: Global Clinical Leader, Daiichi Sankyo

Study record dates

Study Major Dates

• Study Start (Actual): November 26, 2019
• Primary Completion (Actual): November 8, 2021
• Study Completion (Actual): February 13, 2024

Study Registration Dates

• First Submitted: July 8, 2019
• First Submitted That Met QC Criteria: July 8, 2019
• First Posted (Actual): July 10, 2019

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: HER2; Human epidermal receptor 2 positive; Unresectable or metastatic; Prior treatment regimen included trastuzumab
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immunoconjugates; Trastuzumab; Trastuzumab deruxtecan
• Other Study ID Numbers: DS8201-A-U205; 2019-001512-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No